Is GPATCH11 p.Glu61Ala (c.182A>C) pathogenic?

GPATCH11 p.Glu61Ala (c.182A>C) is classified Uncertain significance in GPATCH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely benign (0.1621); Very rare (popmax 8.72e-05%, nfe).

How common is GPATCH11 p.Glu61Ala (c.182A>C) in the general population?

GPATCH11 p.Glu61Ala (c.182A>C) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about GPATCH11 p.Glu61Ala (c.182A>C)?

AlphaMissense predicts likely benign (score 0.1621) — an in-silico prediction, not a clinical call.

GPATCH11 p.Glu61Ala

c.182A>C · rs1249766988 · VCV2330345

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1621 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1621	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -9.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.92 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 7,878 bp · p 0.23 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E83A vs ClinVar E61A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,147,052 alleles

Overall 0.000193% 3/1,551,984 alleles · very rare exomes 3/1,399,650 · genomes 0/152,334 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00332%	30,090
European (non-Finnish)grpmax	8.72e-05%	1,147,052

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GPATCH11
Protein: p.Glu61Ala
Coding: c.182A>C
MANE Select: NM_174931
dbSNP: rs1249766988
Type: single nucleotide variant
Location: chr2:37089762 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.60
Residue 83 UniProt numbering: the 'disordered' region

Full GPATCH11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPATCH11 p.Ala146Ser Uncertain significance ★ ⚠ same type
GPATCH11 p.Ala36Val Uncertain significance ★ ⚠ same type
GPATCH11 p.Ala46Val Uncertain significance ★ ⚠ same type
GPATCH11 p.Arg152Gln Uncertain significance ★ ⚠ same type
GPATCH11 p.Asn75Lys Uncertain significance ★ ⚠ same type
GPATCH11 p.Asp10Glu Uncertain significance ★ ⚠ same type
GPATCH11 p.Asp177Gly Uncertain significance ★ ⚠ same type
GPATCH11 p.Asp208Glu Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/gpatch11-p-glu61ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown